A Phase 2 Study of Tazemetostat in Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma With EZH2 Gene Mutation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 28
- 主要终点
- Objective Response Rate (ORR) Based on Independent Reviewer Assessment
研究概览
简要总结
This is a multicenter, open-label, Phase 2 study to assess the efficacy and safety of tazemetostat in participants with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL) with EZH2 gene mutation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with histological diagnosis of B-cell non-Hodgkin's lymphoma (NHL) as follows:
- •Cohort 1: Follicular lymphoma (FL)
- •Cohort 2: Diffuse large B-cell lymphoma (including primary mediastinal B-cell lymphoma and transformed FL)
- •Participants who have confirmed EZH2 gene mutation of tumor in central laboratory
- •Participants who have measurable disease
- •Participants who had previous therapy with systemic chemotherapy and/or antibody therapy and for which no standard therapy exists
- •Participants who had progressive disease or did not have response (complete response or partial response) in previous systemic therapy, or relapsed or progressed after previous systemic therapy
- •Participants with Eastern Cooperative Oncology Group performance status of 0 to 1
- •Participants with life expectancy of ≥3 months from starting study drug administration
- •Participants with adequate renal, liver, and bone marrow function
- •Male and female participants ≥20 years of age at the time of informed consent
- •Participants who has provided written consent to participate in the study
排除标准
- •Participants with prior exposure to EZH2 inhibitor
- •Participants with a history or a presence of central nerves invasion
- •Participants with malignant pleural effusion, cardiac effusion, or ascites retention
- •Participants with allogeneic stem cell transplantation
- •Participants with medical need for the continued use of potent inhibitors of Cytochrome P450 3A (CYP3A)or potent inducer of CYP3A (including St. John's wort)
- •Participants with significant cardiovascular impairment
- •· Participants with prolongation of corrected QT interval using Fridericia's formula to > 480 milliseconds (msec)
- •Participants with venous thrombosis or pulmonary embolism within the last 3 months before starting study drug
- •Participants with complications of hepatic cirrhosis, interstitial pneumonia or pulmonary fibrosis
- •Participants with active infection requiring systemic therapy
- •Women of childbearing potential or man of impregnate potential who don't agree that both the participant and his/her partner will use a medically effective method for contraception for periods from before informed consent to during the clinical study and 30 days later (for males 90 days later) from last administration of study drug
- •Woman who are pregnant or breastfeeding
- •Participants who were deemed as inappropriate to participate in the study by the investigator or sub-investigator
- •Have any prior history of T-cell lymphoblastic lymphoma/T-cell acute lymphoblastic leukemia or myeloid malignancies, including myelodysplastic syndrome
研究组 & 干预措施
FL with EZH2 gene mutation
Participants with follicular lymphoma (FL) with the EZH2 gene mutation will receive oral tazemetostat at a starting dose of 800 milligrams (mg) twice daily (1600 mg total daily dose) by continuous regimen, no less than 8 hours between doses.
干预措施: Tazemetostat (Drug)
DLBCL with EZH2 gene mutation
Participants with diffuse large B-cell lymphoma (DLBCL) with the EZH2 gene mutation will receive oral tazemetostat at a starting dose of 800 mg twice daily (1600 mg total daily dose) by continuous regimen, no less than 8 hours between doses.
干预措施: Tazemetostat (Drug)
结局指标
主要结局
Objective Response Rate (ORR) Based on Independent Reviewer Assessment
时间窗: From date of first dose of study drug administration to date of PD or death, whichever occurred first (up to 3 years 4 months)
ORR was defined as percentage of participants with confirmed best overall response (BOR) of complete response (CR) or partial response (PR) using independent reviewer assessment based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. BOR of CR and PR was confirmed by a subsequent CR assessment and CR or PR assessment. CR: disappearance of all measurable, non-measurable lesions and no unequivocal new lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (\<) 10 millimeter (mm). PR: at least a 30 percent (%) decrease in sum of diameters (SOD) of target lesions, taking as reference the baseline SOD and there are no unequivocal new lesions, and no progression of non-target disease. The 2-sided 95% confidence interval (CI) was calculated by Clopper-Pearson method.
ORR Based on Investigator Assessment
时间窗: From date of first dose of study drug administration to date of PD or death, whichever occurred first (up to 3 years 4 months)
ORR was defined as percentage of participants with confirmed BOR of CR or PR using investigator assessment based on RECIST 1.1. BOR of CR and PR was confirmed by a subsequent CR assessment and CR or PR assessment. CR: disappearance of all measurable, non-measurable lesions and no unequivocal new lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis \<10 mm. PR: at least a 30% decrease in SOD of target lesions, taking as reference the baseline SOD and there are no unequivocal new lesions, and no progression of non-target disease. The 2-sided 95% CI was calculated by Clopper-Pearson method.
次要结局
- Progression-free Survival (PFS) Based on Independent Reviewer Assessment(From date of first dose of study drug administration to date of PD or death, whichever occurred first (up to 3 years 4 months))
- PFS Based on Investigator Assessment(From date of first dose of study drug administration to date of PD or death, whichever occurred first (up to 3 years 4 months))
- Duration of Response (DOR) Based on Independent Reviewer Assessment(From the date of first confirmed objective response (OR) to PD or death due to confirmed PR or CR (up to 3 years 4 months))
- Number of Participants With Any Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(From the first dose of study drug to 30 days after the last dose (up to 3 years 5 months))
- DOR Based on Investigator Assessment(From the date of first confirmed OR to PD or death due to any cause for those participants with a confirmed PR or CR (up to 3 years 4 months))
- Time to Response (TTR) Based on Independent Reviewer Assessment(From the date of first dose until date of first observation of CR or PR (up to 3 years 4 months))
- TTR Based on Investigator Assessment(From the date of first dose until date of first observation of CR or PR (up to 3 years 4 months))